TRANSLATE BIO, INC.

Patent Trials and Appeals Board

Jun 16, 2021

2020004768 (P.T.A.B. Jun. 16, 2021)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
14/521,351 10/22/2014 Michael Heartlein MRT-1120US1 4498
147667 7590 06/16/2021
Translate Bio, Inc.
c/o Proskauer Rose LLP
One International Place
Boston, MA 02110
EXAMINER
MARVICH, MARIA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
06/16/2021 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
docketingpatentboston@proskauer.com
intellectualproperty@translate.bio
oandrews@proskauer.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MICHAEL HEARTLEIN, FRANK DEROSA, and
LIANNE SMITH1
Appeal 2020-004768
Application 14/521,351
Technology Center 1600
Before ERIC B. GRIMES, TAWEN CHANG, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of treating Argininosuccinate Synthetase Deficiency, which have
been rejected as nonenabled. We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

1 Appellant identifies the real party in interest as Translate Bio, Inc. Appeal
Br. 2. We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42.
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STATEMENT OF THE CASE
The Specification states that “Argininosuccinate Synthetase
Deficiency (ASD) is an autosomal recessive metabolic genetic disorder
characterized by a mutation in the gene for the enzyme argininosuccinate
synthetase (ASS1), affecting its ability to bind to citrulline, aspartate and
other molecules.” Spec. ¶ 2. The Specification also states that “[d]efects in
the ASS protein disrupt the urea cycle and prevent the liver from properly
processing excess nitrogen into urea,” leading to “[a]n accumulation of
ammonia and other byproducts of the urea cycle (such as citrulline) [which]
is toxic.” Id. “The present invention provides, among other things, improved
methods and compositions for the treatment of Argininosuccinate Synthetase
Deficiency (ASD) based on mRNA therapy.” Id. ¶ 3.
Claims 1, 4, 6–9, 11, 13, 15, 17, 19, 20, and 33–36 are on appeal.
Claim 1, reproduced below,2 is illustrative:
1. A method of treating Argininosuccinate Synthetase
Deficiency (ASD), the method comprising
administering intravenously to a subject with the ASD a
composition comprising an mRNA-loaded liposome at an
effective dose and administration interval to treat the ASD;
wherein the administering results in reduced ammonia
levels in a blood sample from the treated subject as compared to
a baseline ammonia level before treatment;
wherein the mRNA encodes an human argininosuccinate
synthetase (ASS1) and comprises a nucleotide sequence at least
90% identical to . . . SEQ ID NO:3;
wherein the liposome has a diameter less than about 100
nm; and

2 The nucleotide sequence of SEQ ID NO:3 has been omitted from the
reproduced claim.
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wherein the liposome comprises one or more cationic
lipids, one or more non-cationic lipids, one or more cholesterol-
based lipids and one or more PEG-modified lipids.

OPINION
Claims 1, 4, 6–9, 11, 13, 15, 17, 19, 20, and 33–363 stand rejected
under 35 U.S.C. § 112(a)4 on the basis that
the specification, while being enabling for a method of treating
a human subject with ASD wherein the method comprises
directly administering a composition to the liver of the human
subject or to an animal subject by intravenous administration
wherein the composition comprises an mRNA encoding ASS1
encapsulated within a liposome comprising cationic lipid, non-
cationic lipid, cholesterol PEGylated lipid in a ratio of
40:30:20:10 by molar ratio at an effective dose and an
administration interval to treat at least one symptom of ASD
but does not enable any other use.
Ans. 3.
As we understand it, the Examiner’s position is that the claimed
method is enabled for non-human animal subjects for intravenous
administration (as claimed) as long as the ratio of lipids in the liposomes is
40:30:20:10 with respect to cationic lipid, non-cationic lipid, cholesterol-
based lipid, and PEGylated lipid, respectively; and is enabled with respect to

3 The statement of the rejection in the Answer refers to “[c]laims 1–20”
(Ans. 3) but the Non-Final Action mailed Nov. 16, 2018 correctly referred to
“[c]laims 1, 4, 6–9, 11, 13, 15, 17, 19, 20 and 33–36” (Non-Final Action 3).
We therefore understand the rejection to apply to all of the pending claims.
4 The Examiner cited 35 U.S.C. § 112, first paragraph, but the instant
application has an effective filing date later than September 16, 2012, so the
provisions of the America Invents Act apply.
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human subjects for direct administration to the liver with the recited ratio of
lipids in the liposomes.
The Examiner, however, rejects the claims on the basis that the
Specification does not enable those skilled in the art “to make or use the
invention commensurate in scope with the[] claims.” Ans. 3. The Examiner
finds that “[t]he scope of the invention is extremely broad” with respect to
both the lipids in the recited liposomes (“the liposome is simply one
comprising one or more cationic lipids, one or more non-cationic lipids, one
or more cholesterol lipids and one or more PEG-modified lipids”) and the
method of administration (“the means of administration of the composition
is any”). Ans. 4.
The Examiner finds that the Specification discloses “formulation of
ASS1 mRNA in a specific formulation.” Id. at 4–5 (citing Spec. ¶ 176). The
Examiner finds that the Specification also discloses that “male CD-1 mice of
6–8 weeks were administered [ASS1 mRNA] by single bolus-tail vein
injection. Plasma [ammonia] levels in the mice were assessed following
administration and levels shown in Figure 11.” Id. at 5.
The Examiner finds that “[t]he art has taught that delivery of naked
nucleic acids as delivery vehicles is a failure.” Ans. 5–6 (citing Sahin5 and
McIvor6). (The Examiner cites numerous references when explaining the
basis of the rejection, but cites the references only by the name of the first
author; the Examiner does not provide complete citations by journal name,

5 The Examiner actually cites Sercombe but the quoted text is found is Sahin
(Sahin et al., “mRNA-based therapeutics — developing a new class of
drugs,” Nature Reviews – Drug Discovery 13:759–780 (2014)).
6 McIvor, “Therapeutic Delivery of mRNA: The Medium Is the Message,”
Molecular Therapy 19(5):822–823 (2011).
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volume, and page number. We have considered the cited references if
Appellant provided them as exhibits attached to the Appeal Brief or if they
could be readily identified in the record. We have not reviewed all of the
references in the record to try to identify the evidence relied on by the
Examiner; establishing a prima facie case of unpatentability includes
identifying the evidence that is asserted to support the prima facie case. See
In re Wright, 999 F.2d 1557, 1561–62 (Fed. Cir. 1993) (“[T]he PTO bears
an initial burden of setting forth a reasonable explanation as to why it
believes that the scope of protection provided by th[e] claim is not
adequately enabled . . . ; this includes, of course, providing sufficient reasons
for doubting any assertions in the specification as to the scope of
enablement.”). We have not considered the references that the Examiner
refers to as “Saffari et al” (e.g., Ans. 7) or “Narang et al., 2013” (Ans. 9).)
The Examiner finds that, “[t]o this end, the art and specification
propose use of lipids to encapsulate and protect molecules being
introduced.” Id. at 8. The Examiner finds, however, that Appellant “claim[s]
the liposome formulation quite generically,” while “[t]he need for
formulation and chemical specificity is critical for the method.” Id. (citing
Yamamoto7).
The Examiner finds that “[l]iposomes encounter multiple defense
systems such as reticuloendothelial system which is the main site of
liposome accumulation following systemic administration, enhanced
permeability and retention, accelerated blood clearance and immunogenicity

7 Yamamoto et al., “Current prospects for mRNA gene delivery,” Eur. J.
Pharm. Biopharm. 71:484–489 (2009).
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aimed [at] elimination of invading substances.” Id. at 9 (citing Sercombe8).
The Examiner also finds that “non-specific effects in non-target cells are an
issue creating an obstacle for gene therapy.” Id. (citing Wang9).
The Examiner finds that “animal models while sufficient for proof of
principle . . . [are] insufficient in regards of how to deliver.” Ans. 9. The
Examiner cites Martinez10 for a description of the factors affecting
“liposomal target site drug delivery.” Id. In this regard, the Examiner finds
that “[t]he liver presents hard to reach targets. However, applicants have not
clarified how or if the remaining obstacles of degradation, side-effects,
clearance and immune response are overcome by the methods.” Id. at 10.
The Examiner also finds that “the mouse model of the specification
and results touted by applicants are a reference to those successful uses.
However, this ignores the teachings of the art that the same methods are not
enabled in humans.” Id. The Examiner acknowledges that “[t]his technology
sees some uses when drugs and other medicines [are] delivered by blood
such as doxorubicin and irinotecan” (id., citing Sercombe) but finds that
“methods based upon delivery of drugs differ greatly from methods of
delivery of nucleic acids” and “the art has not demonstrated success in use of
liposomes in humans by intravenous administration.” Id. at 10–11.

8 Sercombe et al., “Advances and Challenges of Liposome Assisted Drug
Delivery,” Frontiers in Pharmacology, Vol. 6, Article 286, pages 1–13.
9 Wang et al. “N-acetylgalactosamine functionalized mixed micellar
nanoparticles for targeted delivery of siRNA to liver,” Journal of Controlled
Release 166:106–114 (2013).
10 Martinez, “Factors Influencing the Use and Interpretation of Animal
Models in the Development of Parenteral Drug Delivery Systems,” The
AAPS Journal 13(4):632–649 (2011).
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The Examiner states that “[w]hat is at issue is the mode of
administration. The art is clear that intravenous/systemic administration of
nucleic acids and proteins is not adequate in its current state to deliver the
molecules to the target site.” Id. at 14. That is, the Specification’s “animal
model is not sufficient to demonstrate that well-known and documented
obstacles in intravenous delivery” have been addressed, and “one of skill in
the art . . . would have had no basis to reasonably predict or conclude that
one could administer ASS1 mRNA in any form by any route such that the
claimed invention would succeed.” Id. at 12. The Examiner concludes that
the claimed method is not adequately enabled by the Specification. Id. at 14–
15.
Appellant argues that the Examiner’s prior art citations “ignore the
simple fact that the Applicant has successfully demonstrated intravenous
administration of the lipid-encapsulated mRNA encoding ASS1 in an
animal model of ASD.” Appeal Br. 10. Appellant argues that Example 3 of
the Specification “showed that a single bolus tail-vein injection of mRNA-
loaded liposomes comprising human ASS1 mRNA resulted in delivery of
ASS1 mRNA and expression of human ASS1 protein in the liver.” Id. at
11.
Appellant also argues that “Example 5 of the instant application
demonstrates that a single bolus intravenous injection of lipid nanoparticle
(LNP) encapsulated ASS1 mRNA into the ASD mouse model resulted in
‘plasma ammonia levels [that] were reproducibly reduced for at least 24
hours following treatment. . . .’” Id. at 12 (alteration in original). Appellant
concludes that “[t]hese data prove that intravenous delivery of lipid-
encapsulated mRNA encoding human ASS1 can be both successfully
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delivered to the animal and result in a clinically relevant output in the
treatment of ASD, namely reduction of plasma ammonia levels.” Id. at 13.
Appellant argues that “bolus tail vein injection is an art recognized
model for intravenous injection in humans.” Id. (citing Wajima11). Appellant
concludes that, at the time the claimed invention was made, “it was well
recognized that bolus intravenous administration in animals could be
extrapolated to humans.” Id. at 14.
Appellant argues that the Examiner improperly dismissed the data
provided in the Specification, and “[t]he Examiner’s position is legally
incorrect as absolute certainty is not a requirement for the extrapolation of
animal data. . . . The Federal Circuit is clear that animal data is sufficient to
enable claims directed to human treatment, and further that human testing is
not required.” Id. at 14–15 (citing Nelson v. Bowler, 626 F.2d 853 (CCPA
1980) and In re Brana, 51 F.3d 1560 (Fed. Cir. 1995)).
Appellant concludes that the “claimed invention is treatment of ASD
by ‘administering intravenously’ a composition comprising an ASS1
mRNA-loaded liposome. The present application clearly describes how to
make a composition comprising an ASS1 mRNA-loaded liposome and how
to intravenously administer such a composition into a subject in need of
treatment.” Id. at 16. Thus, Appellant contends, the enablement requirement
of 35 U.S.C. § 112(a) has been met.
We agree with Appellant that the Examiner has not met the burden of
showing that undue experimentation would be required to practice the

11 Wajima et al., “Prediction of Human Pharmacokinetic Profile in Animal
Scale Up Based on Normalizing Time Course Profiles,” J. Pharm. Sci.
93(7):1890–1900 (2004).
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claimed invention. “[T]he PTO has the initial burden of challenging a
presumptively correct assertion of utility in the disclosure.” In re Brana, 51
F.3d at 1566. (Although the Brana court referred to utility, the rejection on
appeal was for lack of enablement under 35 U.S.C. § 112, first paragraph. Id.
at 1564.)
“Section 112 requires that the patent specification enable those skilled
in the art to make and use the full scope of the claimed invention without
undue experimentation.” Invitrogen Corp. v. Clontech Labs. Inc., 429 F.3d
1052, 1070 (Fed. Cir. 2005) (internal quotation marks omitted). However,
“[u]sefulness in patent law, and in particular in the context of
pharmaceutical inventions, necessarily includes the expectation of further
research and development. The stage at which an invention in this field
becomes useful is well before it is ready to be administered to humans.” In
re Brana, 51 F.3d at 1568.
Appellant’s Specification states that “administration of an mRNA
encoding a human ASS1 protein, encapsulated within a liposome, resulted in
highly efficient and sustained protein production in vivo and successful
reduction of plasma ammonia levels, a clinically-relevant disease marker.”
Spec. ¶ 3. This assertion is supported by, at least, the Specification’s
Example 3 and Example 5.
The Specification’s Example 3 describes an experiment in which mice
were injected (“a single, bolus intravenous injection”) with human ASS1
(hASS1) mRNA-loaded lipid nanoparticles. Spec. ¶ 183. The Specification
reports that “a clear dose response was achieved when measuring liver levels
of human ASS1 protein,” with ASS1 protein levels below the limit of
detection for doses of 0.10 and 0.30 mg/kg; 546 ng/mg total protein for a
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dose of 0.6 mg/kg; up to 3371 ng/mg total protein for a dose of 2.0 mg/kg.
Id. ¶ 184, Table 1.
The Specification states that “[t]hese data demonstrate the ability of
the lipid nanoparticles to accumulate in the liver and release the mRNA
payload and the liver to process this exogenous mRNA via translation to
produce human ASS1 protein.” Id. ¶ 184.
The Specification’s Example 5 is said to “demonstrate[] that
administration of ASS1 mRNA results in successful reduction of plasma
ammonia levels.” Id. ¶ 196. The Specification states that “ASS1 knockout
mice were administered 1.0 mg/kg of ASS1 mRNA lipid nanoparticles . . .
or empty lipid nanoparticles once every 14 days for 30 days.” Id. ¶ 197.
“Prior to each dose on days 1, 15 and 29, plasma samples were collected
(i.e., pre-dose). Plasma samples were also collected within 24 hours
following each dose[,] on days 2, 16 and 30. Additional plasma samples
were collected on days 8 and 22.” Id. The Specification’s Figure 11 is
reproduced below:

Figure 11 shows plasma ammonia levels for untreated wild-type (WT)
mice, untreated ASS1 knock-out (KO) mice, ASS1 knock-out mice
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administered empty lipid nanoparticles (NP), and ASS1 knock-out mice
administered lipid-encapsulated ASS1 mRNA (ASS1 MRT).
The Specification states that the results “demonstrated that plasma
ammonia levels were reproducibly reduced for at least 24 hours following
treatment to levels near those observed in wild-type mice.” Spec. ¶ 197. This
statement is supported by Figure 11, which shows that ASS1 knock-out mice
administered lipid-encapsulated ASS1 mRNA had greatly lowered plasma
ammonia levels on days 2, 16, and 30, following administration of the
mRNA on days 1, 15, and 29.
In short, the Specification provides working examples demonstrating
the effectiveness of the claimed method in a mouse model of ASD, which
provides a reasonable basis for concluding that the same intravenous method
of administration could be successfully used in a human patient. On this
point, Wajima discloses “a method for predicting the concentration–time
profile in humans based on pharmacokinetic data for animals. The method is
based on the assumptions that concentration–time profiles of a drug are
similar among species.” Wajima 1890, abstract. Wajima also discloses that
“the assumption of the similarity of concentration–time profiles among
species was found to be acceptable” for the drugs used, and “[t]his method
can be applied to any drug on the assumption that normalized curves from a
variety of species can be superimposed.” Id.
The Examiner acknowledges that the claims are enabled for
intravenous administration to an animal subject, but finds that they are only
enabled for direct administration to the liver for a human subject, and in both
cases only for “an mRNA encoding ASS1 encapsulated within a liposome
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comprising cationic lipid, non-cationic lipid, cholesterol[,] PEGylated lipid
in a ratio of 40:30:20:10 by molar ratio.” Ans. 3.
The Examiner, however, points to no persuasive evidence in the
record, and provides no persuasive technical reasoning, to support the
position that a specific ratio of cationic lipid, non-cationic lipid, cholesterol-
based lipid, and PEGylated lipid in the recited liposomes is necessary to
avoid undue experimentation. See Ans. 4–15. At best, the Examiner states
that “[t]he need for formulation and chemical specificity is critical for the
method.” Id. at 8.
In support, the Examiner cites Yamamoto’s statement that “the design
of novel cationic polymers for mRNA delivery has to carefully address
nucleic-acid binding strength and efficient cationic polymers used for pDNA
delivery may not be suitable for mRNA delivery.” Id. (emphasis added). The
claimed method, however, is not directed to using cationic polymers for
mRNA delivery, but instead uses liposomes made up of four specific types
of lipids. The Examiner’s position that the claims are only enabled for
liposomes made of a cationic lipid, a non-cationic lipid, a cholesterol-based
lipid, and a PEGylated lipid in a molar ratio of 40:30:20:10 is not supported
by the evidence.
We also disagree with the Examiner’s position that “[t]he scope of the
invention is extremely broad in that the liposome is simply one comprising”
the four enumerated types of lipids, and “[s]econdly, the claims are broad in
that the means of administration of the composition is any.” Ans. 4. First, the
claims are limited to intravenous administration, so the Examiner’s
statement that “the means of administration of the composition is any” (Ans.
4) is incorrect.
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Second, we do not agree that the scope of the claims is “extremely
broad.” Claim 1 requires intravenous administration of an mRNA at least
90% identical to a specified sequence (SEQ ID NO:3), in liposomes that are
smaller than 100 nm in diameter and made up of four specified types of
lipids, to a subject with Argininosuccinate Synthetase Deficiency, at a dose
and administration interval that is effective to treat the ASD and reduce
plasma ammonia levels relative to the level before treatment.
With regard to the working examples and guidance in the
Specification, the Examiner acknowledges only a single formulation of
ASS1 mRNA. Ans. 4–5 (quoting Spec. ¶ 176). However, the Specification’s
paragraphs 168 to 175 also show formulations of ASS1 mRNA that appear
to meet the limitations of claim 1; thus, the Specification exemplifies nine
specific formulations, not just the one acknowledged by the Examiner.
The Examiner also acknowledged the results of the Specification’s
Example 5, as shown in Figure 11. Ans. 5. The Examiner found that “[t]he
results are a little confusing as the levels rise and fall over the days.” Id. As
discussed above, however, the results shown in Figure 11 show that ASS1
knock-out mice had reduced plasma ammonia levels on days 2, 16, and 30,
following administration of lipid-encapsulated ASS1 mRNA on days 1, 15,
and 29. Thus, we do not find the results shown in Figure 11 to be confusing.
What seems to be critical to the Examiner’s rejection is the “[s]tate of
the art.” Ans. 5. The Examiner finds that “[t]he art has taught that delivery of
naked nucleic acids as delivery vehicles is a failure.” Id. The Examiner cites
McIvor and Sahin in support.12 Id. at 5–7. However, the claims are not

12 The Examiner also cites a reference by “Saffari et al” but, as noted above
(supra at 4–5), this reference was not identified with specificity and we do
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directed to delivery of naked nucleic acids, but to delivery of mRNA-loaded
liposomes.
The Examiner acknowledges that “the art and specification propose
use of lipids to encapsulate and protect molecules being introduced.” Ans. 8.
But the Examiner finds that “the method has faced numerous obstacles
generically in animals and at all [sic] in humans.” Id. (citing Sercombe). The
Examiner also finds that “[l]iposomes encounter multiple defense systems
such as reticuloendothelial system which is the main site of liposome
accumulation following systemic administration, enhanced permeability and
retention, accelerated blood clearance and immunogenicity aimed [at]
elimination of invading substances.” Id. at 9 (citing Sercombe).
As we understand it, the Examiner’s position is that the prior art
shows that liposomal delivery of active agents to human subjects faces
obstacles that would require undue experimentation to overcome in order to
effectively treat a disorder. We do not agree that the cited evidence supports
the Examiner’s position.
The Examiner cites Sercombe in support of her position. The Examiner
cites Sercombe’s statement that “[d]espite considerable research in the last 50
years and the plethora of positive results in preclinical studies, the clinical
translation of liposome assisted drug delivery platforms has progressed
incrementally.” Ans. 8 (citing Sercombe, abstract). This statement, however,
refers to a “plethora of positive results in preclinical studies,” and states that
“liposome assisted drug delivery . . . has progressed,” albeit “incrementally.”
We do not agree that these statements indicate that practicing the claimed

not find it in the record. We have not considered the “Saffari et al.”
reference.
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method in a human subject would require undue experimentation, especially
in view of Sercombe’s statement that
[t]he application of liposomes to assist drug delivery has
already had a major impact on many biomedical areas. They
have been shown to be beneficial for stabilizing therapeutic
compounds, overcoming obstacles to cellular and tissue uptake,
and improving biodistribution of compounds to target sites in
vivo.
Sercombe, abstract.
The Examiner also finds that Sercombe discloses that “[l]iposomes
encounter multiple defense systems such as reticuloendothelial system
which is the main site of liposome accumulation following systemic
administration.” Ans. 9. Sercombe, however, indicates that “[t]he RES is the
main site of liposome accumulation following their systemic administration.
Primary organs associated with the RES include the liver, spleen, [etc.]. . . .
The liver exhibits the largest capacity for liposomal uptake followed by the
spleen.” Sercombe 3, right col. The claimed method is based on delivery of
mRNA-loaded liposomes to the liver. See Spec. ¶¶ 183–184. Thus, we do
not agree that the reticuloendothelial system would be expected to be an
obstacle to successfully practicing the claimed method.
The Examiner also cites Sercombe’s disclosure that other obstacles to
successfully administering liposomes include “enhanced permeability and
retention, accelerated blood clearance and immunogenicity aimed
elimination of invading substances.” Ans. 9. The Examiner has not,
however, pointed to evidence showing that the issues identified by Sercombe
are limited to human patients. Appellant has shown that the claimed method
can be successfully carried out in mice (Spec. ¶¶ 182–197), and the
Examiner has acknowledged that the claimed method is enabled for non-
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human animal subjects (Ans. 3). The Examiner has not provided persuasive
evidence that the obstacles identified by Sercombe would necessitate undue
experimentation in humans, even though they would not do so for other
species.
The Examiner finds that “[t]he art has established that animal models
while sufficient for proof of principle i.e. does the mechanism behind the
efficacy of therapy work, is insufficient in regards of how to deliver.” Ans.
9. The Examiner quotes a passage from Sahin, but that passage addresses
“IVT mRNA,” or in vitro transcribed mRNA, not liposome-encapsulated
mRNA. Id. The Examiner also finds that “Martinez details these issues in
liposomal target site drug delivery,” but none of the cited or quoted passages
addresses liposomal drug delivery. See id. at 9–10.
The Examiner finds that “[t]he liver presents hard to reach targets.”
Id. at 10. The Examiner does not, however, cite any evidence in support of
this finding, and it is contradicted by Sercombe’s disclosure that “[t]he RES
is the main site of liposome accumulation following their systemic
administration” and “[t]he liver exhibits the largest capacity for liposomal
uptake.” Sercombe 3, right col.
The Examiner acknowledges that “[t]his technology [liposomal
delivery] sees some uses when drugs and other medicines [are] delivered by
blood such as doxorubicin and irinotecan (see Sercombe et al page 7).” Ans.
10. The Examiner finds, however, that “methods based upon delivery of
drugs differ greatly from methods of delivery of nucleic acids.” Id. The
Examiner does not cite any evidence in support of this finding, nor does she
provide persuasive reasoning to support the position that, even though small
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molecule drugs are successfully delivered via liposomes, the same would not
be expected for mRNA.
In summary, Appellant’s Specification provides working examples
showing successful practice of the claimed method in a mouse model of
ASD, and the Examiner has not provided persuasive evidence to show that
the claimed method would not be expected to be successful in human
subjects without the need for undue experimentation. The rejection of claims
1, 4, 6–9, 11, 13, 15, 17, 19, 20, and 33–36 under 35 U.S.C. § 112(a) for
lack of enablement is not supported by a preponderance of the evidence in
the record, and is therefore reversed.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 4, 6–9,
11, 13,
15, 17,
19, 20,
33–36
112(a) Enablement 1, 4, 6–9,
11, 13,
15, 17,
19, 20,
33–36

REVERSED